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I. Syngenta Comments on Preliminary Work Plan

(1) Syngenta comments in response to EPA statements: Guideline Number 835.4100, 

Aerobic soil metabolism; Page 4, Table 1.

Enclosed with this submission is data that has not been previously submitted to EPA to address 

this anticipated data need.

EPA Response: 

EFED received the referenced study/overview under MRID numbers 49139001 and 49139002 

and the study is under review. Until the review is complete and the study is classified as 

acceptable, the anticipated data requirement for OSCPP Guideline 835.4100 remains. 

A quick examination of the submitted study shows that the level of un-extracted/un-identified 

residues increases to a range of 28-48%. Furthermore, it appears that not all of EFED’s concerns 

about the un-extracted residues were addressed in the referenced submittals. Please refer to Unextractable Residues section on pages 19 to 22 of the Registration Review Preliminary Problem 

Formulation document and EFED conclusion: “In the absence of data on identity/toxicity of unextracted residues, these residues will be included as part of the stressor.”

(2) Syngenta comments in response to EPA statements: Guideline Number 835.4400, 

Anaerobic aquatic metabolism; Page 4, Table 1.

This anticipated data need is being addressed within the enclosed data submitted herein.

EPA Response:

As stated previously, EFED has received an overview document of an anaerobic and aerobic soil 

metabolism study (MRID 4913900). [EFED concurs with Syngenta’s statements on page 4 of the 

referenced overview document concerning the anticipated data requirements for an anaerobic 

aquatic study. On page 4 of this is overview document, Syngenta stated: “Regarding the 

proposed data gap for the anaerobic aquatic sediment metabolism (EPA Guideline835.4400), 

Syngenta concurs with the EPA that degradation of prometryn under these conditions is very 

likely to be long (essentially stable) as found under anaerobic soil metabolism conditions 

(included within the new aerobic soil metabolism study being submitted). Thus, Syngenta accepts 

the EPA's proposal to deem prometryn stable under anaerobic aquatic sediment conditions 

rather than conduct a new study.]
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Based on the information provided by Syngenta, EFED will assume that prometryn is stable under 

anaerobic aquatic sediment conditions. Therefore, the anticipated data requirement for an anaerobic 

aquatic study is no longer needed for the prometryn registration review.

II. Syngenta Comments on Registration Review Problem Formulation for Prometryn

(1) Syngenta Comment in response to EPA statement, “Furthermore, there are fifteen 24C 

Special local need (SLN) labels;” Page 6, Section 2, 2nd paragraph. 

There is a Caparol 4L 24C label in OR for control of weeds on the following crops grown for 

seed: carrots, parsley, and coriander (EPA SLN No. OR-040002) that is not included in the list 

provided. 

EPA Response: 

EPA will update the list of SLN registrations when the PRA is initiated. 

(2) Syngenta Comment in Response to EPA Statement, “Pre-plant 4 inches incorporated, 

Notes & Restrictions.” Celery/Direct seeded crop; Product(s), Notes & Restrictions: 

Caparol 4L, Prometryn 4L, Cotton-Pro, and Prometryne 4L (Agri-solutions/

Loveland); CA only 

The Caparol 4L label specifies that this use pattern may be used in AZ, CA, and NM only. We 

believe that this should be reflected in the Notes & Restrictions Column. 

EPA Response: 

The Agency has verified that the current Syngenta Caparol 4 L label (9/27/2001) specifies that 

preplant incorporation is limited to AZ, CA, and NM. EFED will use the most current label 

information for development of the PRA. The Agency will also work with Syngenta (and other 

registrants) to achieve label clarity prior to initiation of the PRA. 

(3) Syngenta Comment in Response to EPA Statement: “Pre- or post-emergence Winter 

application for bedded land to be planted cotton; MSR MYR 1.6” 

The Caparol 4L label allows a maximum single application rate of 2.4 lb AI/A on medium or fine 

soil. We believe that the MSR (maximum single rate) and MYR (maximum yearly rate should be 

listed as 2.4 instead of 1.6. 

EPA Response:
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The Syngenta Caparol 4L label appears to allow a rate of 2.4 lb ai/A for pre-emergence 

application to certain soils (p. 15). The label also states, “Do not apply a second postemergence 

application of Caparol 4L or injury may occur.” EFED will use the most current label 

information for development of the PRA. The Agency will also work with Syngenta (and other 

registrants) to achieve label clarity prior to initiation of the PRA. 

(4) Syngenta Comment in Response to EPA Statement, “Post-emergence directed” and 

“Chemical hoe (emerged weeds only)” (Table 1, rows G & H on pages 7 & 8 of the 

problem formulation) 

On the Caparol 4L label, “chemical hoe” and “lay-by” are meant to be two sub-categories of 

“postemergence-directed.” Specific use rates are not provided under the main heading but 

rather under the sub-headers for “chemical hoe” and “lay-by.” The use patterns in Table, row 

(G) Post Emergence directed are actually for chemical hoe. 

Because of this, we believe that the title for row (G) should be changes from “Postemergence 

directed” to “Chemical hoe (emerged weeds only),” and that row (H) should be removed. 

However, the maximum number of applications for chemical hoe should be changed to 3 and the 

maximum yearly rate should be changed to 1.5 and 2.1. 

EPA Response:

The Agency appreciates Syngenta’s clarification of the Caparol 4L label, the directions for use,

post-emergence directed application, in the comments to the public docket. The problem 

formulation, Table 1, rows (G) & (H) on pages 7 & 8, should read as follows:

The Agency will work with Syngenta (and other registrants) to achieve label clarity prior to 

initiation of the PRA.

(G) Post-emergence directed:

* In cotton 3-6 inches tall, be extremely careful to avoid spray contact with cotton leaves by applying Caparol 4L with a precision applicator 

equipped with fenders or shields;

* In cotton <10” tall, apply only if cotton is bedded or flat-planted.

 (a) Chemical Hoe (emerged weeds only): 

* Minimum cotton plant Height = 3-6” and maximum weed 

Height= <1”;

OR 0.5 3 1.5 NS Use only in AR, LA, MO, MS, TN and TX

* Minimum cotton plant Height = >6” and maximum weed 

Height= <2” 0.7 3 2.1 NS Use in all other cotton regions

 (b) Lay-By (emerged and germinating weeds)

* Minimum cotton plant Height = >12” and maximum and 

weed Height= <2” 1.6 1 1.6 N/A

No use or lower use rates depend on 

location, soil texture, and/or weed size
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(5) Syngenta Comment in Response to EPA Statement, “Lay-By, MSR 1.6; MNA 1; MYR 

3.2” (Table 1 on page 8 of the problem formulation, row I)

In the lay-by section, the Caparol 4L label specifies that this application be made once per 

season. We believe that the MNA (maximum number of applications) should be listed as 1 

instead of 2, and the MYR should be listed as 1.6 instead of 3.2. 

EPA Response: 

EFED concurs with Syngenta’s comment. The rate should be as shown in the Table above (refer 

to item 4, above).

(6) Syngenta Comment in Response to EPA Statement, “Celery/Seedbeds; Product(s), 

Notes & Restrictions: Caparol 4L, Prometryn 4L, Cotton-Pro, and Prometryne 4L 

(Agri-solutions/Loveland); FL only” (Table 4 on page 9 of the PF) 

The Caparol 4L label includes this use pattern under the section “Celery, Chinese celery, 

Florence fennel; Seedbeds;” however, it does not contain a regional restriction that allows this 

application to be made in FL only. We believe that this should be clarified in EFED’s Table 4 so 

that this regional restriction is not listed for Caparol 4L. 

EPA Response: 

Although the Syngenta Caparol 4L labels states no regional restrictions, labels for products 

registered to other companies (EPA Reg. Numbers 34704-692 and 9779-297) bear the regional 

restriction, FL only. The Agency will work with Syngenta (and other registrants) to achieve 

label clarity prior to initiation of the PRA. 

(7) Syngenta Comment in Response to EPA Statement, “Celery/Direct seeded crop; 

Product(s), Notes & Restrictions: Caparol 4L, Prometryn 4L, Cotton-Pro, and 

Prometryne 4L (Agri-solutions/Loveland); CA only” (Table 4 on p.9 of the PF)

The Caparol 4L label includes this use pattern under the section “Celery, Chinese celery, 

Florence fennel; Direct Seeded Crop;” however, it does not contain a regional restriction...for 

CA only. We believe that this should be clarified in EFED’s Table 4 so that the regional 

restriction is not listed for Caparol 4L. 

EPA Response: 

Although the Syngenta Caparol 4L labels states no regional restrictions, labels for products 

registered to other companies (EPA Reg. Numbers 34704-692 and 9779-297) bear the regional 
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restriction, CA only. The Agency will work with Syngenta (and other registrants) to achieve 

label clarity prior to initiation of the PRA. 

(8) Syngenta Comment in Response to EPA Statement, “Celery/Transplanted crop; 

Product(s), Notes & Restrictions: Maximum rate is for HI; lower use rates depend on 

location (Lower rates for CA, TX, FL, MI, OH and WI) and soil texture (Lower rates 

for coarse textured/low OM soils)” (Table 4, page 10 of the PF)

The “Product(s), Notes & Restrictions” column does not specify which product labels contain 

the use pattern, but the application rates listed are inconsistent with those found on the Caparol 

4L label. We believe that the “Products, Notes & Restrictions” column should be revised to list 

which products contain this use pattern and Caparol 4L should not be listed. 

EPA Response: 

Please note that what was listed in Table 4 of the PF covers the maximums for all labels

including labels for products registered to other companies (higher rates and different 

restrictions). However, for Caparol 4L and as per page 24 of the label, the following applies:

(9) Syngenta Comment in Response to EPA Statement, “Celery Group/Chinese celery and 

Florence fennel: Pre crop emergence/at or shortly after planting OR Post crop 

emergence @ 2-5 true leaves crop stage and weeds <2” tall; Product(s), Notes & 

Restrictions: Caparol 4L and Prometryn 4L; CA only” (Table 4, p 10 of PF)

The Caparol 4L label includes this use pattern; however, it does not contain a regional 

restriction. We believe that this should be clarified in EFED’s Table 4 so that this regional 

restriction is not listed for Caparol 4l. 

EPA Response: 

Please note that what was listed in Table 4 of the PF covers all labels including labels for 

products registered to other companies. However, for Caparol 4L and as per page 24 of the label, 

the following applies:

Celery/Transplanted crop: Post-transplant during 

the 2-6 week period after transplanting and weeds 

<2” tall 2.0 1 2.0 NA

For Caparol: Maximum rate is for AZ, CA, 

TX, MI, OH and WI; lower use rates depend 

on location and soil texture (lower rates for FL 

and coarse textured soils and soils with low 

OM

Celery, Chinese celery, Florence fennel: Pre crop 

emergence/ at or shortly after planting OR Post 

crop emergence @ 2-5 true leaves crop stage and 

weeds<2” tall

1.6

OR

1.0

1

1

1.6

1.0

N/A

N/A

No regional restrictions for Caparol 4L but it is 

not to be used on sand or loamy sand soils
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EFED appreciates Syngenta’s comments on the PF and these comments will be taken in 

consideration along with existing label language in determining application parameters for future 

risk assessments. In the PF document, EFED requested additional information concerning the 

use pattern for Caparol 4L (please refer to page 11 of the EFED Registration Review Preliminary 

Problem Formulation), including the following:

(1) The maximum yearly rate for each application type, i.e., the nine application types stated in 

the 1st column of Table 1, above, use site such as “TX” and/or soil (e.g., sandy loam 

soil)/cotton plant height (e.g., cotton 3-6”) /weed size (e.g., Weeds <2”);

(2) Which types of applications may be combined within the year; and

(3) Missing information (marked by NS or ?) which are necessary for exposure modeling and for 

inclusion in future labels.

For SuprendTM Herbicide, the label states “Do not exceed a total of 2.7 lbs./A of Suprend per 

season from all applications” (that is 2.14 lbs a.i “prometryn”/A) and continues to state “Do not 

exceed 5.15 lbs. active ingredient of prometryn per acre per season resulting from all 

applications of SuprendTM or Caparol 4L, or other prometryn containing products”. The 

registrant is requested to modify the statements above to clarify if the seasonal rate or the yearly 

rate is 2.14 lbs a.i of prometryn/A/season “assume: year” or 5.15 lbs a.i of prometryn/A/season 

“assume: year”.” For modeling purposes, EFED assumes the maximum possible number of 

applications/year and the minimum application intervals, if this information is missing. 

Therefore, the information on which applications may be combined is important and a maximum 

rate per year for each crop should be included in the label.

(10) Syngenta comments in response to EPA statements: Aqueous photolysis half-life 

(25°C): Stable; Page 16, Table 6.

Prometryn is photodegraded more rapidly in natural waters with half-lives ranging from 16 to 

109 days, which provides a more realistic input for exposure modeling. Wallace, et al. (2010)1.

EPA Response:

Photolysis in natural waters will be included in characterization; however, as per modeling 

parameters guidance, the aqueous photolysis half-life at 25 oC will be used in modeling. Please 

refer to: http://www.epa.gov/oppefed1/models/water/input_parameter_guidance.htm for more 

information on this guidance. 

(11) Syngenta comments in response to EPA statements: half-lives for Aerobic Aquatic 

Metabolism (total system) in River and Pond Systems; Page 17, Table 7 

There is a third half-life value available, 38 days (EU-FOOTPRINT Pesticide Properties Database 

(Functional TOOls for Pesticide Risk assessment and management) that should be considered. EUFOOTPRINT is a research project funded by the European Commission as part of its 6th Framework 

Programme for Research and Technological Development (FP6). http//www.eu-footprint.org/ppdb.html. 
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Specific data cited here is also found in: Tomlin, C.D.S. 1997. The Pesticide Manual: A World 

Compendium, 11th ed. Publisher: British Crop Protection Council. ISBN 978-1-901396-18-8. 1457 p.)

EPA Response:

The referenced values may be included in characterization; however, only results from 

acceptable studies are used for modeling.

(12) Syngenta comments in response to EPA statements: Soil-Water Partition Coefficients 

(KFOC) L/Kg; Page 17, Table 7 and Statements on mobility of the chemical on Page 18, 

Paragraph 4 (two Comments).

First Comment: There are additional Koc values available for prometryn from a column leaching study 

and in the open literature: 

• EPA guideline Koc values from the batch equilibrium study (MRID 41875901): 246, 169, 117, 

448 mL/g

• EPA guideline Koc value from the column leaching study (MRID 41875904): 1228 mL/g

• Koc values reported by Rao and Davidson (1982)2: 56.9, 100.0, 194.1, 200.0, 202.9, 207.9, 

239.1, 264.7, 272.3, 292.4, 299.4, 320.5, 323.9, 327.3, 348.6, 355.4, 380.4, 386.7, 415.3, 444.4, 

471.2, 503.0, 504.4, 507.9, 508.3, 528.9, 606.5, 607.8, 610.0, 637.5, 826.9, 865.4, 918.6, 1067.6, 

1362.2, 1775.0, 2388.4, 3013.9 mL/g 

• Koc value reported by Seol, et al. (2000)3: 400 mL/g 

• Koc values reported by Baskaran and Kennedy (1999)4: 483, 254, 432 mL/g 

Koc values reported by Turin and Bowman (1997)5 fall in the overall range of soil adsorption 

characteristics, but were not included in the calculation of Koc model input because the individual 

Koc values were not reported in the publication, only the range (190-617 mL/g).

Second Comment: The discrepancies can be explained by correlating organic carbon content for soil 

used in the column leaching study with available Kd values, as the study by Rao and Davidson (1982)2 

indicated that soil adsorption (Kd) correlated linerally with percent organic carbon (%OC). Using the 

linear correlation relationship derived from Rao and Davidson (1982)2 for the California sandy loam 

(0.407% OC) used in the column leaching study, a Koc value of ~1307 mL/g may be calculated. Based on 

batch equilibrium soil adsorption, column leaching and open literature data, prometryn soil adsorption 

ranges between 57 mL/g and 3014 mL/g. Using the mobility classification presented by FAO (2000)6, 

prometryn would range from ‘slightly mobile’ to ‘mobile’. The mean Koc value (577 mL/g) from 

laboratory, batch equilibrium, soil column leaching and open literature data falls in the ‘moderate 

mobility’ class (FAO, 2000)6 and therefore, less likely to be transported into surface and ground waters.

EPA Response: 

EFED will consider the additional Koc Values referenced in Syngenta’s comments when

determining the appropriate adsorption/desorption values for characterization and modeling (Koc

Vs Kd). In this respect, it is noted that only values from acceptable adsorption/desorption studies 

are used for modeling; as per the per modeling parameters guidance.
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(13) Syngenta comment in reference to EPA Statement, “Freshwater fish Acute: 

Rainbow Trout (Oncorhynchus mykiss), 96-hr LC50 = 2.91 mg/L” p. 24, Table 9: 

MRID 0070686 was completed in 1965, prior to the development of standardized test 

guidelines, and hence the methods used for the test were not consistent with current guideline 

specifications. In particular, the prometryn exposure concentrations were not measured, 

dissolved oxygen and pH were not reported, water temperature reached 17.2° C (OPPTS 

850.1075 recommends 12 ± 2 ° C for rainbow trout), and temperature deviated by a range of 

4.4° C in some treatments (OPPTS 850.1075 recommends ± 1 ° C). Syngenta believes that 

data from the more recent rainbow trout acute study (Hamaker 1985a, MRID49076601) are 

more reliable and accurate and therefore should be used in the assessment. The endpoint for 

the Hamaker 1985a study is 5.46 mg/L.

EPA Response: 

MRID 49076601 is currently undergoing Agency review. During the development of the 

preliminary risk assessment (PRA), the Agency will determine which rainbow trout study is 

appropriate for use. 

(14) Syngenta comment in reference to EPA Statement, “Freshwater invertebrate Acute: 

Water flea (Dapnia magna), 48-he EC50 = 9.70 mg/L” p. 24, Table 9: 

Syngenta believes that due to data quality concerns associated with Marchini et al. (1988) 

(e.g., no raw data, no control data, actual exposure treatments not described (neither number 

of treatments nor concentration), test concentration were not analytically confirmed (stocks 

measured but no data provided or discussed and cannot be verified because raw data was 

not provided) that the freshwater invertebrate acute endpoint should be based on data from 

the D. magna GLP study (Hamaker 1985b, to be submitted following these comments).

EPA Response:

The Hamaker 1985b, to be submitted by Syngenta following these comments, will be reviewed 

during the development of the PRA. At that time, the Agency will decide which studies are 

appropriate for use in the assessment. 
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(15) Syngenta comment in reference to EPA Statement, “Green Algae: Selanastrum 

capricornutum 7-d IC50 = 11.6 μg/L” p.25-26, Table 10: 

Syngenta believes that the value should be 23 μg/L as indicated in the study report.

EPA Response: 

The study report indicates the 4-d is IC50 = 11.6 μg/L and the 7-d is IC50 = 23 μg/L. A 4-day 

algal toxicity study is the standard test length used by the Agency and thus the 4-d IC50 will be 

used in the assessment.

(16) Syngenta comment in reference to EPA Statement, “Terrestrial plants Seedling 

Emergence and Vegetative Vigor: Monocots + Dicots EC25 values” p. 28, Table 11: 

There appear to be inconsistencies between the endpoint values in the study reports (MRID 

41035903, 41035904) and those provided in the preliminary problem formulation 9-10. 

Syngenta lists the endpoints in a pending report “Review and Assessment of the Potential 

Impact of Prometryn on Federally Threatened California Red-legged Frog (Rana aurora 

draytonii). The following briefly describes how endpoints were reanalyzed.

An attempt was made to fit three non-linear models (logistic, extreme value and Gumbel) to 

dry weight data from each trial from both the vegetative vigor and seedling emergence 

studies (see Equations 1, 2 and 3 below). In some cases, rate-response was not evident, and 

the sigmoidal (s-shaped) models could not converge with the data. Model fitting was 

conducted with SAS software® (SAS Version 9.1), using the PROC NLIN procedure, a nonlinear regression approach, which minimizes the sum of squared error terms. Rate (lb a.i./A) 

data were log transformed (base 10) based on visual inspection. The measure of effect (dry 

weight) was converted to an estimated response, calculated as the proportion reduction in 

dry weight of each replicate relative to the mean of control replicates for the trial.
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Of the models providing the lowest error (lowest sum of squared error terms (SSE)), the most 

sensitive EC25 metric was selected for each species in each study unless the estimated 

response for the trial was greater than 50% at the first treatment level. If this was the case, 

the trial was not considered for EC25 estimation (this only occurred for the 2nd cucumber 

trial from the vegetative vigor study). A regression approach was taken to fitting parametric 

species sensitivity distributions (SSDs). Median plotting positions were used to assign 

observed proportion of species to the ordered EC25s with Filiben’s approximation to the 

median for inner values (Aldenberg et al., 2002)12. Log logistic, extreme value and gumbel 

models (see Equations 1, 2 and 3) were fit to these observed proportion of species affected 

(EC25s exceeded) versus the rate of deposition (lb a.i./A) using PROC NLIN nonlinear 

procedure in SAS Software (SAS Version 9.1).

Summary of terrestrial plant EC25 estimates for dry weight with various crop species

Study Species Trial EC25 Estimate (lbs 

SE Cabbage 2 0.0155

SE Lettuce 2 0.0578

SE Cucumber 1 0.0768

SE Onion 1 0.110

SE Oat 1 0.115

SE Ryegrass 1 0.179

SE Tomato 1 0.195

SE Soybean 1 0.299

SE Corn 1 0.427

SE Carrot 1 1.99

VV Cucumber 1 0.004

VV Lettuce 2 0.008

VV Cabbage 1 0.085

VV Tomato 1 0.130

VV Onion 1 0.164

VV Soybean 1 0.184

VV Corn 1 0.754

VV Oat 1 1.34

VV Carrot 1 >1.6

VV Ryegrass 1 >1.6

SE = Tier II Seedling Emergence, VV = Tier II Vegetative Vigor

EPA Response: 

The Agency appreciates Syngenta’s analysis of endpoints regarding MRID 41035903 and 

41035904. During the development of the PRA, EFED will rerun the statistics using CETIS, 

updated software, to ensure the derivation of endpoints is consistent across studies. CETIS,
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Comprehensive Environmental Toxicity Information System, is a commercial software program 

designed to statistically compare responses at each tested chemical concentration to the 

responses of the controls in order to determine the NOAEC (No Observed Adverse Effects 

Concentration) and LOAEC (Lowest Observed Adverse Effects Concentration), as well as to 

estimate LC (Lethal Concentration), EC (Effect Concentration), and IC (Inhibition 

Concentration) values at the 5%, 10%, 25%, and 50% levels. CETIS has been specifically 

customized to store and analyze (EFED) study data according to current standard procedures. 

CETIS has replaced all EFED statistical programs used to conduct data evaluation reviews on 

standard laboratory toxicity study data.